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Standardized Measurement of Nasal Membrane Transepithelial Potential Difference (NPD)
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Published on: September 13, 2018

Correlation between nasal membrane permeability and nasal absorption rate.

Hefei Zhang1, Chih-Wei Lin, Maureen D Donovan

  • 1Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, 180 Park Avenue, Florham Park, New Jersey 07932, USA.

AAPS Pharmscitech
|December 11, 2012
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Summary

In vitro nasal permeability (Papp) strongly correlates with in vivo nasal absorption rates (ka) for drug candidates. This finding suggests nasal drug absorption can be predicted using simple in vitro tests.

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Area of Science:

  • Pharmacokinetics
  • Drug Delivery
  • Biopharmaceutics

Background:

  • Nasal drug administration offers a direct route for systemic delivery.
  • Predicting in vivo nasal absorption from in vitro data is crucial for drug development.

Purpose of the Study:

  • To investigate the correlation between in vitro nasal permeability (Papp) and in vivo nasal absorption rates (ka).
  • To assess the utility of Papp as a predictor for nasal drug absorption.

Main Methods:

  • Measured Papp for 11 drug compounds using animal nasal explants.
  • Determined plasma time-concentration profiles after intravenous (IV) and intranasal (IN) administration.
  • Calculated absorption rates (ka) from IN profiles using deconvolution and plasma clearance from IV profiles.
  • Analyzed the correlation between Papp and ka using Pearson correlation.

Main Results:

  • A good correlation (r=0.77) was observed between Papp and ka for the tested compounds.
  • The results indicate a direct point-to-point relationship between in vitro permeability and in vivo absorption.

Conclusions:

  • In vitro Papp measurements from nasal explants can effectively estimate nasal absorption rates (ka).
  • This in vitro method provides a valuable tool for predicting the nasal bioavailability of drug candidates early in development.